Pulsed field ablation device and method

ABSTRACT

An ablation device and method for pulsed field ablation, the device comprising a catheter including an expandable basket, a set of electrodes formed on the expandable basket, and a pulse generator suitable for generating electric pulses wherein the pulse generator being in electrical connection with the set of electrodes. The expandable basket is formed of a braided mesh of filaments, wherein the filaments are made of nonconductive material, wherein at least portion of the filaments comprises a lumen, wherein the filaments further include electrodes and conductive wires. The conductive wires at least partially lead inside of the lumen of the filaments and are electrically connected to the electrodes.

CROSS-REFERENCE TO RELATED APPLICATIONS

This application claims priority to US Provisional Patent ApplicationNos. 63/171,832, filed on Apr. 7, 2021; 63/218,563, filed on Jul. 6,2021; and 63/249,965, filed on Sep. 29, 2021, all of which areincorporated herein by reference in their entirety.

FIELD OF THE INVENTION

This invention relates to ablation devices and methods, specificallydevices and methods of pulsed field ablation of a target tissue bypulsed electric fields where one of the main principles of the ablationmay be an irreversible electroporation of cell membranes.

BACKGROUND OF THE INVENTION

Atrial fibrillation is the most common persistent cardiac arrhythmia,affecting 10% of the population over 60 years of age. In addition topharmacological treatment, the established therapy to improve thesymptoms of the disease and reduce mortality is so-called catheterablation.

Catheter ablation involves subcutaneously advancing one or more flexiblecatheters into the patient's blood vessels, in case of a heart ablationusually either in a femoral vein, an internal jugular vein, or asubclavian vein. The catheters are then advanced towards the targettreatment site in or on the heart.

The primary means of ablation therapy of cardiac arrhythmias is toeliminate the pro-arrhythmogenic substrate directly by destroying it orto prevent the spread of non-physiological action potential by linear orcircular isolation. Both of these approaches basically require theformation of a lesion through which the action potential of themyocardium does not spread. By applying energy, a small part of themyocardium is locally destroyed and is transformed into non-myocardialconnective tissue by natural physiological processes within severalweeks.

Common methods of ablation known from the prior art are based on thermaldestruction of the tissue either by high or by low temperatures. Suchmethods include for example heating a target tissue by radiofrequencyfield (RF) or laser, or freezing the tissue by cryoablation. Thosemethods cause necrosis of the target tissue, which can add risk to theprocedure.

Recently, methods and devices using electric fields for ablation havebeen utilized. The goal of these methods is to cause tissue destructionby inducing an irreversible electroporation of cell membranes instead ofdestruction by high or low temperatures, and so reduce the disadvantagesand risks of ablation procedures based mainly on thermal damage, howeverthere are still drawbacks that need to be solved.

Common design of such devices may be a catheter with a distal tip withone or more electrodes. The catheter can have for example one activeelectrode on the tip. An indifferent electrode can be placed for exampleon the skin of a patient. Ablation of the target treatment site withsuch a device has to be done point by point, which increases theduration and complexity of the procedure.

Another example of a prior device is a catheter with electrodes placedin a row on a distal tip of a single catheter body. The distal tip ofsuch catheter is delivered close to the target treatment site anddeployed (bent) into a specific shape near the target treatment site.With such a shape, more than one electrode can be used for the therapyand less movement with the distal tip is needed, but the deployment ofthe catheter into the right shape, proper positioning and furthermanipulation with such a catheter can be very difficult. An indifferentelectrode can be placed on the skin of the patient as well or theablation can be carried out in bipolar fashion between particularelectrodes placed on the distal end of the catheter.

Devices with catheter terminal baskets comprising single struts withelectrodes are known as well from the prior art. Such a device mayassure easier deployment and positioning against the target site.Because there are usually more electrodes placed on the catheterterminal, the ablation can be again either monopolar with an indifferentelectrode, for example placed on the skin of the patient, or bipolarbetween particular electrodes on the catheter terminal. One disadvantageof this solution is limited struts, which means a limited number ofelectrodes creating a specific circular pattern in space. Thisdisadvantage is caused by a need for mechanical stability of theparticular struts to be able to keep a stable shape of the basket. Thismeans to be rigid enough, the struts need to keep particular dimensions.The number of struts used is then limited by the size of the catheter.Another disadvantage of this solution is such a construction cannotfully assure a mutual distance of the struts in the deployedconfiguration, which means the distance between electrodes cannot beassured as well. That means the device may need to be repositionedmultiple times in order to ensure proper ablation, which prolongs theduration of the procedure.

The quality and safety of the ablation needs to be increased on onehand, while risks for patients and duration of therapy need to bereduced on the other hand. There is thus a need for improved devices andmethods of ablation, which would be more gentle and safer for thepatient, with reduced complexity and with enhanced quality andreliability of the method and device itself.

SUMMARY OF THE INVENTION

Disclosed herein is a device and method of an ablation system, inparticular an ablation method and device for pulsed field ablation byelectric fields according to the description, which can address andsolve the above-mentioned problems, and which would be more gentle andsafer for the patient, with reduced time and technical complexity andwith enhanced quality, efficacy and reliability of the system, methodand device itself.

BRIEF DESCRIPTION OF THE DRAWINGS

An exemplary aspect of the present disclosure is illustrated by way ofexample in the accompanying drawings in which like reference numbersindicate the same or similar elements and in which:

FIG. 1 is a block diagram of an exemplary ablation system.

FIG. 2 is an overview of an exemplary pulsed field ablation device withcatheter.

FIG. 3A shows an exemplary catheter with a shaft assembly.

FIG. 3B is an exemplary representation of a cross-section of a shaftassembly.

FIG. 4 is an exemplary representation of a distal tip of the catheterwith a basket assembly in expanded configuration.

FIG. 5 shows an exemplary distal tip of the catheter with a basketassembly in collapsed configuration.

FIG. 6A shows an exemplary expanded expandable basket.

FIG. 6B is a detail view of an exemplary expandable basket withfilaments.

FIG. 6C is a detail view of an exemplary expandable basket withfilaments and conductive wires.

FIG. 7A is a front view of an exemplary distal tip of a catheter.

FIG. 7B is a side view of an exemplary distal tip of a catheter.

FIG. 8 shows an exemplary braided mesh with elongated electrodes.

FIG. 9 shows an exemplary braided mesh with filaments and conductivewires inside of the lumen of the filaments.

FIG. 10 is an exemplary schematic view of a position of the basketassembly adjacent to a treatment site.

FIG. 11 is a schematic view of an exemplary mode of operation ofelectrodes.

FIG. 12 is a schematic view of another exemplary mode of operation ofelectrodes.

FIG. 13A is an example of a spatial pattern of electrodes on a distaltip of a catheter.

FIG. 13B is another example of a spatial pattern of electrodes on adistal tip of a catheter.

FIG. 14 is a view of a possible layout of electrodes already switchedinto a hybrid operation mode.

FIG. 15A shows an exemplary pattern of electrodes.

FIG. 15B shows another exemplary pattern of electrodes.

FIG. 15C shows another exemplary pattern of electrodes.

FIG. 16 shows a part of an exemplary pulsed field ablation protocol.

FIG. 17 a shows an example of inter-pulse pauses with voltage differentthan 0V.

FIG. 17 b shows examples of different biphasic pulses.

FIG. 18 is a view of one example of a terminal assembly.

FIG. 19 shows another view of an exemplary terminal assembly.

FIG. 20 shows an example of filaments joined together at their crossingpoint.

FIG. 21 is a view of a distal part of the basket assembly with mergedstructures and living hinges.

DETAILED DESCRIPTION

FIG. 1 shows an ablation system (100) for pulsed field ablation of atarget tissue. The ablation system (100) described herein includes apulsed field ablation device (101). The ablation system (100) mayinclude or may be connected to other parts or devices appropriate forperforming or for supporting during performance of a method of thepulsed field ablation described herein. The other parts or devices maybe for example a control unit (111), a graphical user interface (GUI)unit (113), electrical control circuits (115), electrocardiogram (ECG)triggering circuits (117), an ECG recording device (129), ECG electrodes(125), a pacing device (131), catheter signal interconnection circuits(119) and/or an electro physiology (EP) display device (133), which mayinclude an EP recording system. The EP display device may show and/orrecord data from one or more other devices connected to the ablationsystem (100). Further, the ablation system (100) may include a mappingdevice (135), for example three-dimensional (3D) mapping device or areal position measurement (RPM) device, and/or indifferent electrodes(127). The mapping device (135) records EGM (intracardial electrograms)for a place in a space measured for example by a catheter and creates amap of a heart's surface. It may also show a position and orientation ofthe catheter. Other possible methods for measurement of a catheter'sreal position may be via a sensor in a catheter (for example positionmeasurement based on magnetics) or for example using impedancemeasurements on a catheter's electrodes or a measurement based onradiofrequency or a combination thereof. Advantageously, in someexamples, the catheter used for the position measurements is the samecatheter that is used for the ablation.

The pulsed field ablation device (101) includes a pulse generator (103)for generating short high voltage electrical pulses and a catheter (105)suitable for insertion into a cavity of a patient's body with a catheterdistal tip (107) suitable for performing the pulsed field ablation oftarget tissue by pulsed electric fields with a set of electrodes (109).The catheter (105) being in electrical connection with the pulsegenerator (103).

The pulsed field ablation device (101) may include or may be connectedto other parts or devices appropriate for performing or for supportingduring performance of a method of pulsed field ablation describedherein. The other parts or devices may be for example a remote controlunit (111), a graphical user interface (GUI) unit (113), electricalcontrol circuits (115), electrocardiogram (ECG) device including ECGtriggering circuits (117), an ECG recording device (129), ECG electrodes(125), a pacing device (131), catheter signal interconnection circuits(119) and/or an electro physiology (EP) display device (133), which mayinclude an EP recording system. The EP display device may show and/orrecord data from other devices connected to the ablation system (100).Further, the ablation system (100) may include a mapping device (135),for example a three-dimensional (3D) mapping device or a real positionmeasurement (RPM) device, and/or indifferent electrodes (127). Forexample, the pulsed field ablation device (101) may be configured foruse in or on a heart of the patient for example for the treatment of theheart tissue, for example for pulsed field ablation of the heart tissue,for example for pulsed field ablation of a myocardial tissue, forexample for pulmonary vein isolation. Devices and methods disclosedherein may be used in other locations, for example all tubular tissues,organs or vessels in a body or for example tumor sites.

The catheter (105) shown in FIG. 2 includes a shaft assembly (201) and acatheter distal tip (107) located adjacent the distal portion of thecatheter (105). The shaft assembly (201) defines a longitudinal centralaxis (203) of the catheter (105). The catheter (105) may further includea handle assembly (123) and a connection assembly (121). The catheter(105) may be steerable or non-steerable and can be introduced into itsposition for example via an introducer sheath (not shown) and with orwithout help of a guide-wire (not shown).

The connection assembly (121) of the catheter (105) may serve forinterconnection of the catheter (105) with other parts of the ablationsystem (100). The connection assembly (121) may include a singleconnection portion or more spatially separated connection portions. Theconnection assembly (121) may be positioned at the proximal portion ofthe catheter (105) and/or for example may be a part of a handle assembly(123). The connection assembly (121) portion may include for example oneor more electrical connections, mechanical connections, fluidconnections and/or an input for a guide-wire.

The handle assembly (123) may be attached to the catheter shaft assembly(201) and may serve for example for steering and manipulation of thecatheter (105), and/or for precise control of the movement anddeflection of the catheter (105). In order to allow for the steeringfunction, there may be knobs (not shown) connected to steering wires(not shown) that may be attached adjacent to the distal section of thecatheter (105) fed through a separate lumen and connected to a knob or asteering mechanism (not shown) inside the handle assembly (123). Thehandle assembly (123) may further include the connection assembly (121)or one or more connection portions of the connection assembly (121), aswell as other parts for example a grip (not shown) and/or a deploymentmechanism (not shown) to deploy/retract the distal tip basket assembly(401, see FIG. 4 ) and/or expandable basket (409) by means of apush/pull of an inner elongated shaft (301) and/or an outer elongatedshaft (303) relative to each other. The deployment mechanism may includefor example an actuator for actuating the inner elongated shaft (301)against the outer elongated shaft (303) in a longitudinal direction.

FIG. 3A shows the catheter (105) with a shaft assembly (201). The shaftassembly may comprise an outer elongated shaft (303) and/or an innerelongated shaft (301). A cross section of an exemplary shaft assembly(201) in a section A-A shown in FIG. 3B, may include two concentrictubes, the outer tube being the outer elongated shaft (303), the innertube being the inner elongated shaft (301). The shafts can translaterelative to each other in a longitudinal direction along thelongitudinal central axis (203). This translation can for example allowthe deployment/retraction of the expandable basket (409) from acollapsed configuration to a fully expanded configuration and back.

The outer elongated shaft may comprise a proximal portion, a distalportion, and a body extending between a proximal and a distal end. Theouter elongated shaft may be coupled to the handle assembly adjacent toits proximal portion and to the catheter distal tip adjacent to itsdistal portion.

The body of the outer elongated shaft (303) may include one or morelumens (309, 311), extending for instance along its entire lengthbetween the proximal and distal ends. The lumens may be for exampleadapted to lead wires or fluids, for example an irrigation fluid. One ormore of the lumens may be configured to accept one or more of the innerelongated shafts. The body of the outer elongated shaft can be forexample further defined by a proximal section (305) and a midsection(307). The midsection of the body may be designed with a flexible jacketcompared to the proximal section to allow bending and increaseflexibility of the outer elongated shaft. The proximal section forinstance includes a stiffer material jacket to increase the torque andrigidity of the body of the outer elongated shaft. Suitable materialsfor construction of the jacket include, but are not limited to Nylon,TPU, HDPE or PEBA.

The body of the outer elongated shaft may include conductive wires. Theconductive wires may lead through the outer elongated shaft's centrallumen (309), or the outer elongated shaft may include several otherlumens (311), hence one or more of the wires may lead through one ormore of the other lumens (311). For example, the number of other lumensmay match the number of filaments of a braided mesh on the catheterdistal tip, for example if 20 filaments are used in the construction ofthe catheter distal tip, 20 other lumens may be used.

The conductive wires may extend from the basket assembly to theconnection assembly for example adjacent to the handle assembly.

In some aspects, the inner elongated shaft may be configured to slidealong the longitudinal central axis relative to the outer elongatedshaft. Therefore, one or more of the lumens may for instance comprise alow friction liner, for example a polytetrafluoroethylene (PTFE) liner.

Rigidity and torque are important features that the outer elongatedshaft should have, hence laterally above/around the PTFE liner the outerelongated shaft may include for example a braid of a metal or a rigidpolymer wire wrapped around the inner layer of the body, which in someaspects is embedded within the outer jacket of the body, or may comprisea rigid polymer including but not limited to Polyimide, Polyamide,Polyether ether ketone (PEEK) or any other suitable material.

The outer layer of the outer elongated shaft may comprise a laminatedpolymer to provide a seamless, smooth and soft surface. Note that, asmentioned earlier, the outermost layers of the midsection and proximalsection may be formed of different polymers, for example a nylonmaterial could be used on the proximal section, while for example aPEBA, which is more flexible compared to nylon, could be used on theoutermost layer of the midsection. Yet, both sections may have the sameinnermost layers. The outer elongated shaft may have a substantiallyconstant outer diameter along its length.

The Outer Diameter (OD) dimension of the outer elongated shaft may forexample fit the French catheter scale that is commonly used for cathetersizing standardization. The diameter in this scale is defined inFrenches (FR), where 1 mm=3 FR. The scale is usually from a 3 FRcatheter up to a 34 FR catheter. For instance, the diameter of the outerelongated shaft may be between 5 FR to 20 FR, or from 7 FR to 16 FR, orfrom 9 FR to 15 FR. The diameter of the central lumen of the outerelongated shaft can be approximately between 0.1 mm and 5 mm, or 1 mm to4 mm, or 2 mm to 3.5 mm, or 2.5 mm to 3 mm.

The inner elongated shaft may comprise a proximal end, a distal end, anda body extending between proximal and distal ends. The body of the innerelongated shaft may include one or more lumens (313), extending forexample along an entire length between the proximal and the distal endof the inner elongated shaft or can have no lumen. The one or morelumens (313) of the inner elongated shaft may be for example designed toaccommodate a standard guide-wire (not shown) and/or to lead a fluid,for example an irrigation fluid. The diameter of the one or more lumens(313) may be from 0.1 mm to 3 mm, or from 0.5 mm to 1.5 mm, or from 0.9mm to 1 mm, or from 0.94 mm to 0.99 mm. One or more of the innerelongated shafts can be suitable for placing in the one or more lumens(309, 311) of the outer elongated shaft. Dimensions of the innerelongated shaft may be chosen to match the diameter of the designatedlumen of the outer elongated shaft, but still the two structures need toallow their smooth relative translation. That means the outer dimensionsof the inner elongated shaft (301) can be from 0.1 mm to 4.9 mm, or from0.5 mm to 3.5 mm, or from 1 mm to 3 mm, or from 1.28 mm to 2.8 mm.

Since the inner elongated shaft can be suitable for accommodation of aguide-wire inside its lumen, a low friction liner, for example a PTFEliner, of the inner lumen can be used.

As mentioned above, the inner elongated shaft can be translated relativeto the outer elongated shaft to deploy the basket assembly/expandablebasket, hence for instance a braided socket is weaved along the lengthof the PTFE liner creating a body of the inner elongated shaft. Anotheraspect may include a cut hypotube instead of a braid in a body of theinner elongated shaft to improve its flexibility and torque.

Laterally above the layer with the braid or the hypotube, a polymerjacket can be melted/laminated to enhance the softness of the tube andprovide a seamless surface. A variety of polymers could be used for thejacket, exemplary materials may be NYLON, polyether block amide (PEBA),Polyether ether ketone (PEEK) or Polyimide.

The distal tip (107) of the catheter of the example shown in FIG. 4 .further includes a basket assembly (401). The basket assembly (401) maycomprise a basket assembly proximal portion (403), a basket assemblydistal portion (405) and a basket assembly body (407) extending betweenthe proximal and distal portions. The basket assembly body may include acentral body portion (419) spreading around the plane (425) intersectingthe basket assembly in a portion with a highest diameter (in one of itsexpanded configurations) in proximal and distal directions, occupyingabout ⅓ of the basket assembly body. The basket assembly body mayfurther include a distal body portion (421) extending distally from thecentral body portion (419) and proximal body portion (423) extendingproximally from the central body portion (419), each of them occupyingabout ⅓ of the basket assembly body (407).

The basket assembly (401) comprises an expandable basket (409). Thebasket assembly proximal portion (403) may include an attachment of theproximal portion of the expandable basket (409) adjacent to the distalend of the outer elongated shaft (303). The distal portion of the basketassembly (401) may include an attachment of the distal portion of theexpandable basket (409) adjacent to the distal end of the one or more ofthe inner elongated shafts (301) creating a terminal assembly (411).

The terminal assembly (411) may be advantageously designed without, orat least with reduced structures protruding in the distal direction fromthe basket assembly distal portion (405), for example a cap or similarformation. This is especially advantageous in situations where at leastpart of the ablation method needs to be performed on a relatively flattreatment site.

An exemplary solution of terminal assembly may be an overmoldedstructure. Filaments may be fixed to each other and/or to distal end ofthe inner elongated shaft by an overmolding process, creating anovermolded terminal assembly. Another fixation procedure (and/orterminal assembly creating procedure) similar to overmolding may be forexample tipping, where the filaments are at least partially melted andpressed into a pre-shaped mold and so connected together and/or to theinner elongated shaft. A lamination is another example process to fixthe filaments at their distal ends to create a terminal assembly. Theterminal assembly may be created by swaging or crimping of a filament'sdistal ends as well. The filaments may be brought together at theterminal assembly area and swaged or crimped together by for examplesome kind of metal ring.

In another example a terminal assembly may be created as a hingedmechanical structure as shown in FIG. 18 . For example, one or morefilaments may be at their distal end in the area of terminal assemblyfixed to articulated elements (1801), which comprise for example lateralnarrow portion (1803) and distal portion (1805) which is wider thanlateral narrow portion (1803). The lateral narrow portion (1803) may befor example in a form of pin with square, rectangular, circular, oval orother suitable cross section. The distal portion (1805) may have forexample a form of an oval or a circle or in another example of ball orsphere. Other possible shapes of the distal portion (1805) could becylinder, cone, cube or block. It may have one of the dimensions thesame as the lateral narrow portion (1803), for example in case the wholearticulated element (1801) is made out of one piece of sheet-likematerial (metal sheet, polymer sheet) or not (for example in case thearticulated element is casted or forged. The articulated element (1801)may be for example made of metal (for example nitinol) or other materialfor example polymer or thermoplastic. The fixation of filaments to thearticulated elements may be done for example by welding, gluing orcrimping. An area of the connection (1807) may be for example at leastpartially laminated to prevent possible tissue damage and to seal theassembly. The articulated elements are then fixed in a central bulletstructure (1809). This may be for example a hollow structure with cutwindows (1811) suitable for accommodation of the proximal part (1803) ofthe articulated elements (1801). The distal parts (1805) of thearticulated elements are in this case placed in the cavity (1813) insidethe hollow structure. The distal parts (1805) of the articulatedelements may in some examples have dimensions (cross section or width)bigger than dimensions of windows (1811). This prevents slipping of thedistal parts (1805) of the articulated elements (1801) through thewindows (1811) thus holding articulated elements, and together with themthe connection area (1807) and distal parts of the filaments attached tothe central bullet structure (1809). The central bullet structure (1809)may comprise several parts connected together (for example by welding,gluing or other mechanical means like snaps, threading, screws, bolts .. . ). It may have different outer shapes as well, for example acylindrical, spherical or oval. The shape of the cavity (1813) maycorrespond to the outer shape or may differ. The central bulletstructure may include fixation part (1815) for fixation of a distal endof an inner elongated shaft to the central bullet structure. Thefixation part (1815) may have for example a shape of a hollow tubeconnected to the central bullet structure. The fixation part is suitablefor accommodation and/or connection of a distal part of the innerelongated shaft and may allow for a flow and/or redirection of a fluid,for example an irrigation fluid coming out of a lumen of the innerelongated shaft. The fixation part may interfere or may be in mechanicaland/or fluid connection with the cavity (1813). It may be adapted todirect at least part of the irrigation fluid into the cavity of acentral bullet structure for example by apertures (1901) as shown inFIG. 19 .

Such a hinge mechanical structure as described above may allow foreasier radial movement (regarding longitudinal central axis of thecatheter) of the filaments in the area of terminal assembly, which maybe advantageous during manipulation with an expandable basket,particularly with transition (deployment/retraction) between a collapsedconfiguration and one or more expanded configurations.

In case metal parts are used in the design of a terminal assembly, theymay be for example used as electrodes, either for ablation or forsensing or mapping or combination of thereof.

The expandable basket may be attached to the inner elongated shaftand/or to the outer elongated shaft for example by gluing, welding,lamination or by mechanical means.

The expandable basket (409) is for instance configured for transition(deployment/retraction) between a collapsed configuration, shown in FIG.5 , and one or more expanded configurations. The transition(deployment/retraction) can be caused by a pre-tension shape of thebraided mesh (413) and/or filaments (415) and/or by a lineardisplacement of the inner elongated shaft (301) against the outerelongated shaft (303) along a longitudinal central axis (203) of thecatheter (105) or by combinations thereof. Another possibility fordeployment/retraction of the expandable basket (409) may be by a tensionof an additional supportive structure for example an inner coil orballoon (not shown).

The expandable basket comprises filaments braided into a mesh. In thecollapsed configuration, the cross-section of the expandable basket maybe equal or dimensionally close to the cross-section of the outerelongated shaft, though in one aspect the cross-section of theexpandable basket may be smaller than the cross-section of the outerelongated shaft and may depend on the dimensions of the outer elongatedshaft. In the expanded configuration the cross-section of the expandablebasket may be significantly larger than the cross-section of the outerelongated shaft. Fully expanded expandable basket may have a maximumcross-sectional diameter of, for example, from 20 mm to 40 mm or from 22mm to 38 mm or from 25 mm to 35 mm. Such dimensions of a fully expandedexpandable basket may be suitable for example for placement in heartcavities. For larger body cavities, for example, the expandable basketmay have larger dimensions, e.g. from 30 mm to 150 mm, or from 40 mm to120 mm, or from 50 mm to 100 mm. In other situations, a fully expandedexpandable basket having smaller dimensions may be suitable for smallerbody cavities. Such a smaller expandable basket may have dimensions inits fully expanded state for example from 3 mm to 25 mm, or from 5 mm to15 mm, or from 7 mm to 10 mm.

In some aspects, the filaments (415) braided into the braided mesh (413)are not cut adjacent to the distal portion of the expandable basket(409), but the filaments (415) may rather be bent at the distal portionand attached adjacent to the distal portion of the inner elongated shaftcreating a terminal assembly. The bent filaments may then be directedback to the expandable basket (409) or the outer elongated shaft, wherethey can be terminated. FIG. 6A shows the expandable basket (409) ingreater detail with bent filaments in its distal portion (603).

The expandable basket made out of the braided mesh has advantages over aprior art solution with unbraided struts, in that the expandable baskethas higher mechanical stability even while using comparably thinnerfilaments. More filaments in the structure may also allow moreelectrodes to be used. The electrodes placed on the filaments can alsobe distributed more optimally, which means for example they can beplaced closer together or can create a desirable pattern on theexpandable basket. Another advantage of the expandable basket made ofthe braided mesh is the higher mechanical stability of the structurethat can ensure stable and predictable distances between electrodes.

The braided mesh may be heat-treated which may ensure deformations andfixation of such deformations of the filaments. Such deformed filamentsthen ensure that during expansion and collapse of the basket assembly(expandable basket) the crossing points of the filaments (points, wherethe filaments intersect each other) stays relatively stable regarding afilament length. It means the filament crossing points stay at therelatively same filament length distances in the collapsed state as wellas in all expanded states of the basket assembly (expandable basket).What is changing is a mutual angle of the particular filaments creatingthe crossing points (for example from about 2 degrees up to 178 degreesor vice versa). Some kind of minor lengthwise movement of the crossingpoints may not be completely avoided by this process, however it staysin limits where it doesn't compromise dimensional and/or mechanicalstability of the braided mesh. This feature may then for example allowplacement of the electrodes in the crossing points of the filamentsand/or ensure stabile, predictable desired mutual positions ofelectrodes and/or their mutual distances.

Even further structure stability of the expandable basket, made out ofthe braided mesh, may be achieved for example by joining of theparticular filaments (included in the braided mesh) together. Thefilaments may be for example joined together at their mutual crossingpoints. An exemplary solution may be seen in FIG. 20 . The joints (2001)may be fixed (not allowing any mutual movement of the filaments in thejoining point) or interacting (some kind of mutual movement of thefilaments in the joining point is possible). The joining may be achievedfor example by gluing, welding, lamination, bonding, tying (for examplewith some kind of string) or melting. Another option could be tying thefilaments together for example by a ring structure or by crimping. Incase the ring structure is made out of conducting material (for examplemetal), it can serve also as an electrode. The same is true for thecrimping. The metal connector may serve as an electrode as well.

Particular meshes within the braided mesh do not need have to haveuniform size, on the contrary, the sizes of particular meshes maydiffer. The sizes may for example increase from the distal portion andthe proximal portion of the expandable basket (where they may besmallest) in the direction toward the middle part of the expandablebasket, where they may be the largest. In other words, the dimensions ofthe meshes in the central body portion of the basket assembly may belarger than the dimensions of meshes in the proximal and distal bodyportions of the basket assembly. The dimensions may for example increaselinearly or exponentially. The circumference of the meshes in theproximal and distal body portions may be for example between 1 mm to 40mm, while the circumference of the meshes in the central body portionmay be for example between 5 mm to 80 mm. The number of rows of themeshes, creating a complete braided mesh of the expandable basket may bebetween 4 to 40.

Two or more filaments creating a braided mesh and hence expandablebasket may be merged or joined together at their proximal and/or distalends to create a merged structure (2101) in the proximal and/or distalportion of the expandable basket as shown schematically in FIG. 21 .Such a solution may reduce a number of filaments at the proximal and/ordistal portion of the expandable basket. Lowering a number of filamentsentering related structures like the basket assembly proximal portionwhich may include an attachment of the proximal portion of theexpandable basket adjacent to the distal end of the outer elongatedshaft, and/or the distal portion of the basket assembly which mayinclude a terminal assembly may reduce a complexity and/or enhancemechanical stability of those structures hence of the whole basketassembly. It may even help to reduce risk of an ablation procedure, dueto a reduction of the number of members in the structures with reducednumber of filaments. In terms of the filament length the mergedstructure in proximal or distal part of the filament may occupy from 1%to 30% or from 3% to 20% or from 5% to 15% of the total length of thefilament included in the expandable basket. As stated before, thefilaments may be merged in distal or proximal ends of the filaments orin both. In the case where the filaments are merged in both ends, themerged length may be the same on both ends, or it may differ. Relativeto the length of the expandable basket in its collapsed configuration,the merged part of the filaments, either on proximal or distal end ofthe basket, may occupy from 1% to 35% or from 4% to 25% or from 6% to20% of the length of the collapsed basket. The filaments may be mergedfor example by gluing, welding, lamination, bonding, tying or melting.Another option could be joining the filaments together for example bysome kind of tubular structure or by crimping. The tubular structure maybe for example a tube made of metal or polymer or thermoplastic withlumen. In this case the end parts of the filaments would be put throughthe lumen of the tube, fixed there (for example by gluing, welding,lamination, bonding, tying, melting or swaging) and so joined together.Another option could be usage of a multi-lumen tube, made of metal orpolymer or thermoplastic, where each end part of each filament to bejoined would be put through a separate (its own) lumen of themulti-lumen tube, fixed there (for example by gluing, welding,lamination, bonding, tying, melting or swaging) and so joined together.

The diameter of the filaments in the braided mesh may be from 0.2 mm to1 mm or from 0.4 mm to 0.8 mm or from 0.5 mm to 0.7 mm. The number ofthe filaments braided into the braided mesh creating an expandablebasket can vary from 5 to 150 or from 10 to 60 or from 15 to 50 or from16 to 32.

The filaments may be made out of electrically insulating, nonconductivematerial, for example polymers or thermoplastic elastomers like Nylon,Fluorinated ethylene propylene (FEP), Polyethylene (PE), PEBA, PEEK,Polyimide (PI), Polypropylene (PP), PTFE, Polyurethane (PU),Polyethylene terephthalate (PET) or for example Silicon. The materialmay be further reinforced for example by glass fibers. The cross-sectionof the filament may be circular, or alternatively other cross-sectionshapes are possible, for example but not limited to oval, round,semicircular, rectangular, square, flat, or star-shaped. The filaments(415) may be for instance formed of tubes with at least partially hollowstructures with lumen (601) as can be seen on FIG. 6B. Some or all ofthe filaments (415) can be hollow along their entire length or forexample the lumen (601) may be present only in a portion of the lengthof one or more filaments (415). Another aspect may include a braidedmesh (413) comprising a first subset of the filaments (415) includinglumens (601) and another subset of the filaments (415) without lumens,or all of the filaments may be without lumen.

There are further options to enhance a mechanical stability of thefilaments. A use of a multilayer wall may be one of them. The wall ofthe filament may include for example more than one layer of material.Materials of different properties may be used, which in combination mayresult in more mechanically stable wall thus more mechanically stablefilament. Such a combination may use layers made each one from differentmaterial from a group of polymers or thermoplastics, for example fromNylon, Fluorinated ethylene propylene (FEP), Polyethylene (PE), PEBA,PEEK, Polyimide (PI), Polypropylene (PP), PTFE, Polyurethane (PU),Polyethylene terephthalate (PET) or for example Silicon. Anotherpossible option may be usage of layers from the same kind of material,but different subgroups of the materials with different properties foreach layer. Materials used in the particular layers may be furtherreinforced for example by glass fibers.

In another aspect, the filaments may be for example further mechanicallyreinforced by insertion of a mechanical support into a lumen of afilament. Such a mechanical support may be for example in form of strutsplaced in the filament lumen. The struts may be placed into the fulllength of the filament, or in a full length of filament lumen, in thecase that the filament does not have a lumen in its entire length.Another possible option would be to place the struts into only a portionof length of the lumen, thus leaving part of the filament reinforcedwith a strut and another part without a strut reinforcement. The strutsmay be for example made of nitinol, for example with electricalinsulation layer, for example from Polyamide (PA), Polyimide (PI) orPTFE. Other possible materials suitable for struts may be polymers orthermoplastics, for example from Nylon, Fluorinated ethylene propylene(FEP), Polyethylene (PE), PEBA, PEEK, Polyimide (PI), Polypropylene(PP), PTFE, Polyurethane (PU), Polyethylene terephthalate (PET) or forexample Silicon.

Yet another option suitable for further reinforcement of the filamentsis to fill at least part of the lumen of the filament by glue or meltedpolymer or thermoplastic material.

A braided mesh then may be constructed in a way that all of thefilaments included in the mesh may be reinforced or only a portion ofthe filaments included in the mesh may comprise a reinforcement andanother portion of the filaments may be without it.

At least one of the filaments creating a braided mesh may include atleast one place where the structure of the filament is locallymechanically weaker than rest of the filament. Such a place may createso called living hinge (2103), schematically shown in FIG. 21 . Theliving hinges may be useful for defining more or less exact places,where filaments included in the braided mesh, and hence in theexpandable basket bend easier and where the bends on the filamentscreate smaller radiuses (or directly kinks) in comparison with filamentswithout such a living hinge. This may further help in defining a morepredictable shape of the deployed expandable basket in at least one ofits deployed positions. Establishment of such a living hinge on thefilament may include thinning or cutting of part of the filament.Thinning may be done for example by squeezing or thermoforming of aparticular place of the filament. The thinning may be made around wholecircumference of the filament, or only partially. Partial asymmetricalthinning may be advantageous, since such created hinge may define aparticular direction in which the filament bends easier compared toother directions. In one example of the expandable basket, the livinghinges created on the filaments may allow easier bending of thefilaments, and hence the braided mesh, for example in a radial directionfrom longitudinal central axis of the catheter. For example livinghinges creating smaller radiuses or kinks on the filaments in a distalbody portion (421) of the basket assembly body or in an area of terminalassembly may help in the shaping of the expandable basket (basketassembly body) in an area located distally from a plane intersecting thebasket assembly at the portion with the highest diameter (in one of itsexpanded configurations) in a way such that at least some of the distalpart of the basket (in an area of a distal body portion) may form largerangles (radially from elongated axis) compared to a proximal part of thebasket (in an area of a proximal body portion). In extreme cases thedistal part of the basket (in an area of a distal body portion) may forman angle of 90° or more (radially from elongated axis) to achieve anexpanded state where at least part of the expandable basket includingelectrodes becomes longitudinally the most distal part of the catheter,without any other part protruding more distally (for example terminalassembly). Such a configuration may be advantageous for example in anablation of a relatively flat treatment site.

At least one living hinge as described in previous paragraph may beincluded on at least one part of the braided mesh, where the filamentsare merged together (on a merged structure). In this case the livinghinge is a place on the merged structure, which is locally mechanicallyweaker then rest of the merged structure and may be created by thinningor cutting of the merged structure for example after merging. Anotheroption to establish a living hinge on the merged structure, particularlyin the case where the merged structure includes polymer tube and wherethe filaments are merged in the lumen of the tube or in the multiplelumens of multi-lumen tube, is to pre-thin or pre-cut the polymer tubebefore inserting the filaments. Such a pre-thinning of the tube may bedone for example by squeezing, thermoforming or by molding, for exampleinjection molding.

The living hinges may be created in an area of a distal body portion,central body portion and/or proximal body portion of the basket assemblybody. They may be placed for example in a proximal area from 0% to 20%or 0% to 15% or 0% to 10% of the length of the collapsed basket in acase where they are in an area of a proximal body portion. They may beplaced in a distal area from 0% to 20% or 0% to 15% or 0% to 10% of thelength of the collapsed basket in a case where they are in an area of adistal body portion. They may be part of the terminal assembly as well.In a case where they are placed in the central body portion, the hingesmay be placed on a plane intersecting the basket assembly in a portionwith a highest diameter or from −20% to +20% or from −10% to +10% orfrom −5% to +5% distally from this plane or from the center of thecollapsed basket.

The expandable basket may include one or more electrodes or a set ofelectrodes. The electrodes can be configured for at least one ofgenerating an electric field for ablating tissue, or obtaining orsending electrical or other signals, for example signals for tissuemapping, ECG monitoring, impedance measurement and/or detection ofcontact with a tissue. Another function of the electrodes may be servingas markers for an X-ray. The electrodes may be coupled to particularfilaments of the expandable basket. Electrodes can be placed on each ofthe filaments or only on some of the filaments. Each filament comprisingthe electrode may include one or more of the electrodes, for examplefrom 1 to 15, or from 1 to 10, or from 1 to 6, or from 1 to 3electrodes. The electrodes can be of one type or of different types. Theoverall number of electrodes placed on the expandable basket may be from1 to 200, or from 5 to 100, or from 10 to 50, or from 15 to 40, or from20 to 35. Spatial distances between electrodes in the fully expandedconfiguration of the expandable basket may be from 0.1 mm to 15 mm, orfrom 0.5 mm to 10 mm, or from 1 mm to 6 mm, or from 2 mm to 4 mm.

In an example, the electrodes may be placed in areas where the filamentscross each other (filaments crossing points). Such a position may beadvantageous due to the ability to keep a more stable distance betweenelectrodes during different configurations of an expandable basket andsuch a configuration may also advantageously prevent unwanted contactbetween electrodes, especially in cases where the expandable basket isnot in a fully expanded configuration.

Each filament may also include electrodes of one type or differenttypes, or different filaments can accommodate different types ofelectrodes. Different types of electrodes may be understood aselectrodes with different functions, for example ablation electrodes,measurement electrodes and so on, or physically different electrodeswith for example different shape, size, design, materials and so on, ora combination of types of electrodes with different functionality andphysical properties. For example, in configurations with ring-shapedelectrodes placed on the filaments, all electrodes may have the samediameter and may differ in length, so there may be for example two ormore groups of such electrodes, each group having different length. Anumber of electrodes in each of the groups may be the same or maydiffer. In an extreme example, each electrode on the expandable basketmay have a different length. In configurations with ring-shapedelectrodes, such electrodes may have a diameter between 0.2 mm to 3 mm,or from 0.4 mm to 2 mm, or from 0.5 mm to 1 mm, and may have a lengthbetween 0.1 mm to 10 mm, or from 0.2 mm to 8 mm, or from 0.3 mm to 6 mm,or from 0.4 mm to 4 mm.

In one example there may be a first group of 5 to 20 shorter electrodes,with lengths of for example 0.3 mm to 3 mm, and a second group of 5 to30 electrodes which may be longer, for example with lengths from 0.6 mmto 4 mm. Advantageously the electrodes from the first group may be usedfor at least one type of measurement, for example for measurement of anintracardial ECG (EGM), or an ablation, and the electrodes from thesecond group may be used for an ablation, either independently or incombination with the electrodes from the first group.

The electrodes can be placed on the body of the basket assembly. Forexample, the electrodes may be placed on the central or distal bodyportion, in some cases the electrodes may be even placed on the proximalbody portion. Other electrodes may be placed on or in an outer elongatedshaft, inner elongated shaft, catheter distal tip or terminal assembly.In configurations where the electrodes are placed on the elongatedshafts, distal tip or a terminal assembly and where ring-shapedelectrodes are used, then they may have a diameter of 0.2 mm to 10 mm,or from 0.5 mm to 8 mm, or from 1 mm to 6 mm, or from 2 mm to 5 mm andmay have a length between 0.1 mm to 20 mm, or from 0.2 mm to 15 mm, orfrom 0.3 mm to 12 mm, or from 0.4 mm to 10 mm.

The layout of the electrodes on the expandable basket may ensurecontinual, for example circular ablation areas while the expandablebasket is in the expanded position and may create a pattern.

For instance, the layout of the electrodes on the expandable basket mayensure continual, circular ablation areas even while the expandablebasket is held in various expanded positions between a fully collapsedand a fully expanded position and may create a pattern as well.

Additional electrodes, for example the ones placed on or in an outerelongated shaft, inner elongated shaft, catheter distal tip or terminalassembly may be part of the pattern or may be operated independently toother electrodes. For example, electrodes at the area of catheter distaltip or terminal assembly may be used for point-like ablation. There maybe special dedicated electrodes at the area of distal tip or terminalassembly or for example metal parts of the terminal assembly may serveas an electrode, or combination of thereof may possible.

The pattern (701) created by the electrodes (109) may be for example acircular pattern in space around the longitudinal central axis (203) atleast when the expandable basket (409) is in one of its expandedconfigurations as can be seen in FIG. 7A. Other two dimensional orthree-dimensional patterns created by the electrodes (109) are possible.The patterns (701) may be centered around the longitudinal central axis(203) or not. The patterns (701) may have different shapes, includingbut not limited to circular, ellipsoidal, square, rectangle, polygonal,planar or other or the placement of the electrodes (109) on theexpandable basket can be irregular. There can be for example one pattern(701) in one plane or more patterns (701) in one plane or more patterns(701) in different planes.

Patterns created by the electrodes may be positioned on the basketassembly body, particularly on the distal body portion, central bodyportion or proximal body portion as shown in FIG. 7B. Patterns may evenextend into more than one of these portions. For example, for atreatment of a flat treatment site positioned distally from the basketassembly, the pattern of electrodes may be positioned advantageously onthe basket assembly distal portion. Particularly the pattern may bepositioned in a section of the basket assembly bounded by an area makingan angle (703) of 0° to 90° to the central axis (203) in a center of aplane (425) intersecting the basket assembly in a portion with a highestdiameter (in one of its expanded configurations). In someconfigurations, a pattern may be positioned partially on the basketassembly body distal portion and partially on the basket assembly bodycentral portion. In some configurations, a pattern may be positioned ina section of the basket assembly bounded by an area making an angle(705) of 0° to 120° to the central axis (203) in a center of a plane(425). Such placement of the pattern may be particularly advantageousfor treatment of a vessel orifice, for example an orifice of a pulmonaryvein. In situations where the treatment site has a tubular shape, thepattern may be placed on the basket assembly middle portion,particularly in a section of the basket assembly bounded by areas makingan angle (707) of 45° to 135° to the central axis (203) in a center of aplane (425). If a flat treatment site is positioned proximally from thebasket assembly, for example a septum, the pattern of electrodes may bepositioned on the basket assembly proximal body portion or partially onthe proximal body portion and partially on the central body portion,particularly in a section of the basket assembly bounded by areas makingan angle (709) of 90° to 180° to the central axis (203) in a center of aplane (425). Optionally electrodes may be placed in all portions of thebasket assembly, thus creating patterns in all of the portions and onlypatterns necessary or optimal for performing a particular therapy may bechosen to perform the therapy.

Particular patterns may be created by all electrodes placed on theexpandable basket or with just a portion of the electrodes. The patternsmay have different numbers of electrodes in various expanded positionsbetween fully collapsed and fully expanded positions of the expandablebasket. The neighboring electrodes in the pattern may have distancesbetween each other for example 0.1 mm-15 mm, or 0.5 mm-10 mm, or 1 mm-6mm or 2 mm-4 mm.

Electrodes are for example electrically connected to the pulsegenerator, for example with conductive wires. The electrodes may beelectrically or communicatively connected to other units or parts of thepulsed field ablation device as well as for example with the mappingdevice, EP display device, pacing device, ECG recording device, cathetersignal interconnection circuits, ECG triggering circuits, electricalcontrol circuits, GUI unit or remote control unit. Apart from thering-shaped electrodes mentioned before, the electrodes may have any ofmany different shapes, for example tubes threaded around the filaments,coiled metal sheets, square and/or rectangle or other shapes ofconductive materials attached to the filaments. Other possible forms ofelectrodes (109) may be elongated continuous electrodes drawn along thesurface of a portion of the filament (415) in a way they do not touch atcrossing points of the filaments (415) in the braided mesh (413) asshown in FIG. 8 . The electrodes (109) may be attached on the particularfilaments (415) of the expandable basket by any means, for example byway of mechanical attachment, swagging, crimping, gluing, lamination,deposition and/or soldering. The electrodes may be made out of anyelectrically conductive material for example copper, gold, steel,titanium, platinum, platinum-iridium, and so on. In a case where thereis at least one filament made out of conducting material, it could serveas an electrode as well. In a case where the whole conducting filamentis uninsulated the whole filament may serve as an electrode, in case thefilament is for example partially electrically insulated, the bare,uninsulated portion may serve as an electrode.

Conductive wires may provide an electrical connection between theelectrodes and a pulse generator. The conductive wires may be a part ofa structure of the basket assembly (401). For instance, the conductivewires (417) may be positioned at least partially in the lumen (601) ofthe filaments (415) as shown in FIG. 6C or in FIG. 9 . There can be oneor more conductive wires (417) coupled to each of the electrodes, or oneor more electrodes can be coupled to a single leading wire. Theconductive wires (417) may be incorporated into the one of the walls ofthe shaft assembly, for example into the wall of the outer elongatedshaft. The conductive wires can also be positioned in the central lumenof the outer elongated shaft or there can be separate lumens in theouter elongated shaft suitable for the placement of conductive wires.The conductive wires may be terminated adjacent to the electrodes or maylead spatially further along the length of the filament past theelectrode. The conductive wires may for example be positioned along thewhole length of the filaments of the basket assembly. Optionally some ofthe conductive wires (417) may be terminated adjacent to the electrodeswhile others may lead spatially further along the filaments past theelectrode or may be positioned along the whole length of the filamentsof the basket assembly.

In a case where the conductive wires are positioned along the wholelength of the filament, the design solution of the expandable basket,where the filaments are bent and returned to the expandable basket,rather than cut, at the expendable basket's distal end is particularlyadvantageous. Because the particular conductive wires are configured tocarry electrical pulses between electrodes and the pulse generator, aninsulation of the cut filaments with the conductive wires inside wouldbe extremely challenging at the terminal assembly. On the other hand, inexamples comprising bent filaments with conductive wires inside, theinsulation of the terminal assembly can be easily assured.

The material used for conductive wires may be any electricallyconductive material for example copper, stainless steel, steel, nitinol,aluminum, gold, platinum, silver and so on. The conductive wires may beinsulated or uninsulated. The wires may be insulated using any suitablematerial, for example polyimide, polyurethane, polyester,polyvinylchloride (PVC), rubber, rubber-like polymers, nylon,polyethylene, polypropylene, silicone, fiberglass, ethylene propylenediene monomer (EPDM), different fluoropolymers likepolytetrafluoroethylene (PTFE) and so on. The wires may be made of asingle conductor or with a group of conductors, whereas a wire made of agroup of conductors is sometimes called “cable”. In case the wires areinsulated a minimum breakdown voltage of the wire insulation should beat least 100V, or 500V, or 1000V or 4000V or 10000V. The diameter of thewires with insulation may be limited by the dimensions of otherstructures of the device such as for example the filaments and a minimumvoltage it has to be able to carry without risk of breakdown. Typicaldiameter of the wires with or without insulation may be between 0.05 mmand 0.7 mm, or between 0.07 mm and 0.5 mm, or 0.1 mm to 0.3 mm orbetween 0.11 mm to 0.2 mm or between 0.12 mm to 0.18 mm.

The construction of the braided mesh out of electrically insulatingmaterial as described with one or more conductive wires inside hollowfilaments may be particularly advantageous for an ablation system basedon the principle of pulsed field ablation by pulsed electric fields. Thepulsed field ablation method as described further, requires electricfields generated around electrodes. To generate the fields, electricalpulses have to be carried by particular conductive wires between theelectrodes and the pulse generator. When the filaments are electricallynonconductive, and the conductive wires are kept inside the filaments asdescribed herein, the electrical insulation of the particular conductivewires can be ensured even at voltage levels of several kV, for examplefrom 1 kV to 10 kV, carried by the conductive wires. However, an optionof braided mesh with at least one or more filaments made out electricconducting material (for example nitinol, copper, stainless steel,steel, aluminum, gold, platinum or silver) may be possible as well. Suchconducting filaments may be insulated or not or only partially. They notonly that could possibly lead electrical current, but could act as anelectrode (when uninsulated or insulated only partially) and/or as afurther mechanical support of the braided mesh hence the expandablebasket.

Another advantage of a braided mesh made of polymer or thermoplasticelastomer filaments is the ease of manufacturing compared for example toa metallic braided mesh. The braided mesh may be for example made withthe help of a three-dimensional mandrel device. The particular filamentscreating the mesh may be placed over the mandrel in a desired pattern.The filaments may already include the conductive wires. The wholestructure may then be heated up, for example close to the melting pointof a material of the filaments and after that the structure may rapidlybe cooled down. The filaments made of thermoplastic elastomer orpolymers generally require lower temperatures to reach the melting pointover most metals, so the manufacturing process can be faster, moreefficient and can demand less energy input. Another advantage of such amanufacturing process is the conductive wires do not need to be heatedto extreme temperatures, to a degree where the electrical properties ofthe wire may be compromised. This situation can happen, for example whenthe braided mesh is made of the metallic wires, where the mesh wiresalso serve as the electrically conductive wires.

The braided mesh with inserted conductive wires may be attached to theouter elongated shaft and inner elongated shaft creating an expandablebasket and part of the basket assembly. The electrodes may be attachedat the particular filaments of the braided mesh before or after theattachment of the braided mesh to the elongated shafts. The pulsegenerator is a part providing generation of electric signals forcatheter electrodes. The pulse generator may allow settings for exampleof an amplitude, a shape of the electrical pulse and/or a number ofpulses during activation. The pulse generator may diagnose electricalwaveforms to measure power as well. The pulse generator may enablesynchronous operation with an ECG device or another part of the ablationsystem or device.

Further, a method of ablation with the described pulsed field ablationdevice is disclosed.

One method comprises the step of disposing a catheter (105) adjacent tothe treatment site, for example a cardiac chamber, in the patient via ablood vessel. The catheter (105) may be inserted into the blood vesselof the patient percutaneously.

Other support structures and/or devices may be used to help navigate thedistal tip of the catheter to its desired location. Examples of suchdevices include a guide-wire or a sheath. The catheter distal tip may bedelivered proximally to the treatment site in a collapsed state, forexample through a sheath. In the collapsed state the diameter of thebasket assembly at the catheter distal tip may be less than orapproximately equivalent to the diameter of the outer elongated shaft ofthe catheter. Such a configuration allows easy access of the catheterdistal tip proximal to the treatment site.

The treatment site may be for example located inside the body, forexample in or on a heart, for example in a heart cavity, particularlyfor example in a left atrium of the heart. The treatment site may forexample include a pulmonary vein orifice. Other locations of thetreatment site may be for example all tubular tissues, organs or vesselsin a body or for example tumor sites.

When the catheter distal tip is delivered to the treatment site, thebasket assembly of the catheter is deployed from the collapsed orsemi-collapsed configuration to one of the expanded configurations. Thisdeployment may be caused by a pre-tension shape of the braided mesh orits filaments or by a linear displacement of the inner elongated shaftagainst the outer elongated shaft along a longitudinal central axis ofthe catheter, by a tension of an additional supportive structure forexample an inner coil or balloon (not shown), or by a combination ofthereof.

The catheter distal tip (107) may then be placed adjacent to a targettissue of the treatment site (1001), for instance at least part of thebasket assembly (401), and/or part of the expandable basket (409) isbrought in contact with the treatment site (1001). In this position atleast a portion of the set of electrodes (109), placed on the basketassembly (401) may be in contact with the tissue of the treatment site(1001). A schematic of an example position can be seen in FIG. 10 . Theterminal assembly (411) may improve contact of the electrodes with thetreatment site by its flat design without distally protrudingstructures. When there are no distally protruding formations on thebasket assembly (401), especially on the basket assembly distal portion(405), it is easier to get the electrodes in contact with the treatmentsite even in situations where the treatment site is relatively flat.

After positioning the catheter distal tip adjacent to the treatment sitean optional step of measurement can be carried out with or without thecatheter. Different kinds of measurements can be performed with the goalof, for example, diagnostics of type or quality of a tissue at or aroundthe treatment site, spatial position of the catheter distal tip,particularly for example the spatial position of the catheter distal tipagainst the treatment site, contact of the catheter distal tip and/orparticular electrodes with the target tissue of the treatment site orwith a goal of understanding electrophysiological processes of a tissueadjacent to the electrodes. For example, the electrodes may be used fora measurement of contact with a target tissue as well and may be placedon the expandable basket, for example on the filaments of the braidedmesh. The measurement electrodes may be different electrodes than theablation electrodes or the ablation electrodes may be used for themeasurements. It is possible to combine separate measurement electrodeswith the ablation electrodes with measurement functions on one catheterdistal tip as well. A separate measurement device may be used to carryout the measurement step, for example a separate measurement catheter(not shown), an ECG device including ECG triggering circuits, an ECGrecording device, ECG electrodes, an intracardial ECG (EGM), anintracardial echo device, an esophagus temperature measurement device, afluoroscopy device, RTG device, MR device, and so on. The measurementstep may be carried out once or may be repeated several times during anablation procedure.

The ablation of the target tissue of the treatment site (1001) forinstance uses a principle of pulsed field ablation caused by pulsedelectric fields of proper parameters. Although the terms “electricfields” or “pulsed electric fields” are mentioned here, electric fieldsas contemplated herein may further comprise a magnetic component.

The procedure of basket assembly deployment, measurements and ablationcan be carried out in several stages. For example, the expandable basketmay be delivered adjacent to the treatment site in a fully collapsedconfiguration. After delivery it can be deployed to its first expandedconfiguration. For example, the pre-tension shape of the braided meshand/or filaments may cause this first transition. In this configurationfor example further manipulation with the basket assembly can be carriedout as well as measurements and/or ablation. Further repositioning,measurement and/or ablation can be carried out in this position in anyorder as well.

Then the basket assembly may be deployed into a second expandedconfiguration. The second expanded configuration can be achieved forexample by a linear displacement of the inner elongated shaft againstthe outer elongated shaft along a longitudinal central axis of thecatheter. In this configuration for example further manipulation of thebasket assembly can be carried out as well as measurements and/orablation. Further repositioning, measurement, and/or ablation can becarried out in this position in any order as well.

The basket assembly can be for example deployed into several differentexpanded positions, during which further repositioning, measurementand/or ablation can be carried out.

In the case of pulmonary vein isolation ablation the set of electrodesmay create a circular shape around the pulmonary vein orifice. After theablation the shape of the ablated tissue may have a circular shapearound the pulmonary vein orifice as well. Several such shapes ofablated tissue may be created by repositioning the basket assembly or byswitching between different electrodes.

The pulsed electric field (PEF) is for instance created by electricalpulses, for example high frequency electrical pulses. The electricalpulses may be generated by a pulse generator and may be delivered to thetarget tissue by the electrodes which may be placed on the catheterdistal tip and which may be in electrical contact with the pulsegenerator. The electrical pulses can be created by a wide variety ofelectrical pulses ranging from monophasic (single polarity) pulses tosymmetrical and/or asymmetrical biphasic pulses. The pulses may becombined with extra pre-pulses for tissue conditioning or extrameasurement pulses as well. Pulses can be single pulses, or they may berepeated in trains, where parameters of the pulses may vary or remainconstant. Trains of pulses can be run in sequences as well. A maximalamplitude of the pulses may depend on the target tissue, electrode'ssize and/or electrode's distance in order to create an electric fieldwith a maximum electric field magnitude for example between 0.1 kV to 10kV or between 0.4 kV to 5 kV or between 0.5 kV to 2 kV per centimeter ina target tissue volume. A duration of the pulse can be from a nanosecondrange to milliseconds range, for example from 2 ns to 10 ms, or from 10ns to 5 ms or from 10 μs to 1 ms. The shape of the pulse may be forexample a square, a curve similar to exponential discharge, a rectangle,a saw, a triangle or a sinusoidal shape.

The pulses can be monophasic or biphasic. Biphasic pulses can besymmetrical or asymmetrical. The pulses can repeat from 1× to 100000×.The frequency of the high frequency pulses may vary from 0.1 Hz to 10Hz. Amplitude (Um) of the monophasic pulses can vary from 100V up to 10kV, and the peak-to-peak amplitude of biphasic pulses may vary from 200Vto 20 kV.

FIG. 16 may serve as an example of a possible part of a pulsed fieldablation (PFA) protocol and as a clarification of terms and expressionsregarding the PFA protocol. The PFA protocol includes a series ofelectrical pulses (1601) and pauses (1603, 1607, 1615). The electricalpulses (1601) may be further organized in units with a certain hierarchylike trains (TR) and bursts (B).

The electrical pulse (1601) may be defined for example by shape,amplitude (Um) with certain voltage and pulse length with time duration(t1). The pulse amplitude (Um) may be either negative or positive (thepulse may have negative voltage or positive voltage) in case ofmonophasic pulses. The electrical pulses (1601) may be separated fromeach other by an inter-pulse pause (1603), which is defined by a timeduration (t2) and a voltage (Up). The voltage during the inter-pulsepause (1603) may drop to 0V or it may have a positive or negativevoltage value (Up). The absolute voltage value (Up) of the inter-pulsepause is smaller than an absolute voltage (amplitude (Um)) of theadjacent electrical pulse (1601), particularly up to 50% of theamplitude (Um) of the adjacent electrical pulse. In situations where theelectrical pulse has a positive amplitude (Um), the voltage value (Up)of the inter-pulse pause (1603) will stay positive between 0V and theelectrical pulse (1601) amplitude (Um), and in situations where theelectrical pulse (1601) has a negative amplitude (Um), the voltage value(Up) of the inter-pulse pause (1603) will stay negative between 0V andthe electrical pulse amplitude (Um). An example of inter-pulse pauses(1603) with a voltage different than 0V is shown in FIG. 17 a . Biphasicpulses may be symmetrical or asymmetrical in at least one of time,amplitude or energy.

Examples of biphasic electrical pulses are shown in FIG. 17 b . Thebiphasic pulses may have the same amplitude (voltage) of a positivephase (1701) and a negative phase (1703) with the same duration (t10,t12) of both phases (exemplary pulse A, D), or the amplitude and/orduration (t10) of the positive phase and the amplitude and/or duration(t12) of the negative phase may differ (exemplary pulses B, C). Theresulting pulses then may have the same energy in the positive andnegative phases of the pulse, or the energy in the positive and negativephases of the pulse may be different. Biphasic pulses with the sameenergy in both phases may be called symmetrical biphasic pulses.Symmetrical biphasic pulses may be balanced (in case the duration andamplitude of both phases of the pulse are identical, or imbalanced (incases where the amplitude and/or duration are different in each phase).Asymmetrical biphasic pulses have phases with different energies.Exemplary biphasic pulses A, B, C are without a pause between particularphases (inter-phase pauses) of the pulse, exemplary pulse D is abiphasic pulse with an inter-phase pause (1705). The duration of theinter-phase pause of the pulse may be from 0 μs to 50 μs or from 0 μs to10 μs or from 0 μs to 5 μs.

A series or sequence of pulses in a row, with or without inter-pulsepauses may be called a train (TR). Particular trains (TR) may becharacterized for example by a time duration (t4), or number of pulsesand may be separated from one another by inter-train pauses (1607) witha time duration (t5) or the inter-train pause (1607) may separate atrain with an individual single pulse. A series or sequence of thetrains (TR) and inter-train pauses (1607) can be called a burst (B), andmay be characterized for example by a time duration (t6), number oftrains (TR), number of pulses or by inter-burst pause (1615) (with timeduration (t7) between particular bursts (B).

As already stated above, a voltage value (Up) at the electrodes may notdecrease to 0V between pulses, particularly during inter-pulse pauses(1603) but may remain at a level, where the risk of creating bubbles byelectrolysis or temperature increment is either non-existent or verysmall, for example up to 50% of the amplitude (Um) of an adjacentelectrical pulse. This may reduce an unwanted relaxation of the polarmolecules as well, which may lead to shorter length of at least someparts of the PFA protocol and so increase an efficacy of the PEFtherapy.

When pulses with amplitude (Um) of hundreds of volts to a few thousandvolts are applied, there is a certain risk of causing a ventricularmuscle depolarization and unwanted ventricular rhythms in the heart,even when applied in a heart atrium. Depolarization can be causeddirectly by electric field or by secondary energy induction in anotherdevice, for example a catheter, which is placed in or near either atriaor ventricles or both. Setting the timing of the active sequences(individual pulses, trains and/or bursts) with pauses described belowresults in an effect called overdrive. The overdrive effect is commonlyused in ablation catheterization procedures to suppress a risk ofunwanted heart rhythms by using an external pacemaker. An advantage ofthe proposed PFA protocol is that the therapeutic (ablation) electricalpulses may, in a case where they cause a myocardium depolarization, alsoact as pace stimulation pulses for the heart, and therefore it is notnecessary to use an additional pacing device (for example an externalpacemaker) to synchronize pulses of the pacing device with thetherapeutic pulses of the PFA protocol. This in turn means that in thiscase it is not necessary to use a pacing device to control the number ofventricular contractions per minute, detect the individual ventricularcontractions from a surface ECG and then trigger the ablation pulsesaccordingly.

The duration (t8) of one cycle (1609) of a burst (B), and inter-burstpause (1615) between bursts, which is between 201 ms to 800 ms, is givenby a range between the need to deliver pulses safely faster than thepatient's actual heart rate (the overdrive effect) and the need tomaintain heart rate at a safe level (which is stated to be approximately220 beats per minute minus age). The cycle duration may be fixed orvariable in the stated range (201 ms to 800 ms) within a PFA protocol,for example according to a sinusoidal or triangular function. Theindividual burst (B) may have a duration (t6) from 1 ms to 200 ms, or 30ms to 180 ms, or 60 ms to 160 ms, which is a safe time to contract theheart chamber by an applied burst (B) of pulses, protecting ventriclesfrom injury or unwanted rhythm. The burst (B) duration (t6) may too befixed or variable in the stated range (1 ms to 200 ms) within a PFAprotocol, for example according to a sinusoidal or triangular function.

This PFA protocol may have other positive effects on the ablationresults, for example reducing the risk of causing an unwantedventricular rhythm and/or maximized PEF application efficiency.

However an electroporation is described as the primary trigger of deathof the myocardial cells after application of the PEF, but actual celldeath may alternatively be caused for example by electrical breakdown ofthe membrane of cardiomyocytes, mitochondria or nucleus; by tearingindividual cells/cardiomyocytes (or groups of cells) of the myocardiumapart (for example, by damaging the intercalated discs, either directlyby electric fields or by mechanical damage by hypercontraction); bydamage to sarcolemma or myofibrils of muscle fiber; by depletion andinsufficient production of ATP in cardiomyocytes due tohypercontraction; by loosening of intercellular junctions ofcardiomyocytes; by muscle cell myolysis; by wrinkling cardiomyocyteseither directly under the influence of the electric field or bymechanical damage by hypercontraction; by irreversible damage to thecalcium cycle (whether by non-physiological function of the sarcoplasmicreticulum or ion pumps or calcium channels or calcium binding proteins);by calcium overload of the heart muscle-mitochondrial swelling (as aresult of hypercontraction or damage to cardiomyocyte sarcolemma ornon-physiological function of calcium channels); or by formation ofreactive oxygen species (ROS) and subsequent oxidation of membranephospholipids by PEF.

The electric fields may be created among one or more electrodes placedon the catheter distal tip and one indifferent electrode placed in thedistance, for example on the skin of the patient. The indifferentelectrode may in some aspects have a significantly larger surface thanthe sum of the surfaces of the active distal tip electrodes. This modeof action is usually called monopolar. Another option for creating anelectric field is in a bipolar mode. In this mode the electric fieldarises between two or more, usually closely-placed or adjacent distaltip electrodes with different polarities. In this case the sum of thesurfaces of active electrodes with the first polarity is similar to thesum of the surfaces of the active electrodes with the second polarity.

In some aspects, the electrodes (109) placed on the distal assembly maybe operated in a hybrid mode of the previous two types. An example ofsuch a mode is shown in FIG. 11 . Only the electrodes (109) placed onthe distal tip (107) are used for ablation in this mode. There is afirst single electrode, or group of electrodes operating in a mode withfirst polarity (P1) and a second single electrode or group of electrodesoperating in a mode with different polarity (P2) (which may be anopposite polarity) than the operating mode of the first electrode orgroup of electrodes. A surface or a sum of the surfaces of the firstelectrode or the first group of electrodes is significantly smaller thana surface or a sum of the surfaces of the second electrode or group ofelectrodes. For example, there may be a third group of electrodesoperating in a third mode in state of high impedance (HI), wherein theimpedance of the electrodes in the third group is for example higherthan 500 SI The electrodes operating in the third mode may be adjacentto the electrode or group of electrodes operating in the first mode.

One advantage of the operation of electrodes in this hybrid mode is thatthe generated electric field will have a more homogenous current densityin comparison to bipolar mode. Another advantage of the hybrid operationmode is the electric fields created in this mode may in some aspects beable to reach deeper into the target tissue compared to bipolar mode. Incase of ablation of a heart cavity, the depth of the ablated targettissue, (in one example the target tissue may comprise a myocardialtissue), may be up to 5 mm.

A variant of the hybrid mode of operation of the electrodes (109) with agroup of electrodes (more than one electrode) operating in the mode withthe first polarity (P1) is shown in FIG. 12 . The functional principleof this mode of operation is similar to the variant with one electrode(109) operating in the mode with the first polarity (P1). For example,the sum of surfaces of the electrodes operating in the mode with thefirst polarity (P1) is significantly smaller than the sum of surfaces ofthe electrodes operating in a mode with a different polarity (P2).

Examples with a group of electrodes (more than one electrode) operatingin a mode with a first polarity (P1) can have an advantage over exampleswith a single electrode operating in the mode with the first polarity(P1) for example in situations where it is advantageous to reduce thesize of the electrodes. Reducing the size of the electrodes can beadvantageous or necessary in cases where it is necessary or desirable toincrease the number of electrodes. A higher number of electrodes isdesirable for example where more precise mapping of the treatment siteor more precise and/or more homogenous ablation of the target tissue ofthe treatment site is desired. Because the treatment site can be part ofa human anatomy, the overall size of the pulsed field ablation device,especially the catheter with a catheter distal tip must be restrictedaccording to human anatomy. It follows that if more electrodes areneeded for the ablation device, then for a certain number of electrodesthe size of the electrodes must be limited to able to fit into therestricted dimensions of the critical parts of the pulsed field ablationdevice for example the catheter and/or its distal tip, and/or its basketassembly. Another advantage of the smaller size of the electrodes isthat such an arrangement may help to increase a depth of the ablation.

Smaller size of the electrodes can have other advantages, for example inexamples where the same electrodes are used for ablation and formeasurements, it means the same electrode must be configured to deliverhigh voltage pulses and record measurements. For example, in measurementof ECG signals, smaller electrodes may be advantageous.

There are however some challenges associated with smaller electrodes aswell. In examples including pulsed field ablation, the electric fieldsare for instance created by electrical pulses, for example highfrequency electrical pulses generated by a pulse generator. Foreffective ablation of the whole target area of the treatment site, itmay be important to create an electric field with a maximum electricfield magnitude of several hundred volts to several kilovolts percentimeter in a target tissue volume. Using smaller electrodes means asmaller surface area of the electrodes. With a smaller surface area ofthe electrodes, the voltage induced on the electrode has to be highercompared to bigger electrodes with larger surface area to achieve thedesired electric field density in a target tissue. Adverse effects ofsuch a configuration may include higher density of the electric field,higher intensity of the electric field and/or possible sparking on theedges of the electrodes. However, using a chosen group of electrodes(more than one electrode) operating in the mode with the first polarityinstead of one electrode operating in the mode with the first polaritycan address and overcome some or all of these issues. With a well-chosenfirst group of electrodes operating in the mode with the first polaritytogether with the second group of electrodes operating in a mode withdifferent polarity and possibly with a third group of electrodesoperating in a third mode in the state of high impedance, the firstgroup of electrodes and/or the second group of electrodes may act asvirtual electrodes. That means the electrodes in the first group may acttogether as one virtual electrode and/or the electrodes in the secondgroup may act as another virtual electrode. With such a configuration,the intensity and/or the density of the electric field near theelectrodes may be reduced. Other positive effects of this configurationmay be a reduced risk of sparking and increased depth of ablation, orincreased depth of an ablated tissue at the treatment site.

The enlargement of the surface area of the electrodes in the first groupand the creation of the resulting virtual electrode may cause areduction in the voltage needed to be induced in the electrodes and/orelimination of sparking, mainly on the edges of the electrodes. However,the concept of disproportional surface areas of the electrodes in thefirst and the second groups of electrodes can be preserved, which meansthe surface area or a sum of the surface areas of the first electrode orthe first group of electrodes is significantly smaller than a surfacearea or a sum of the surface areas of the second electrode or group ofelectrodes. The ratio of the surface area of the electrode or the sum ofthe surface areas of the electrodes in the first group to the sum of thesurface areas of the electrodes in the second group of electrodes may bebetween 2:3 to 1:100, or 3:5 to 1:80, or 3:5 to 1:70, or 1:2 to 1:50, or1:2 to 1:40, or 1:2 to 1:30, or 1:2 to 1:20, or 1:3 to 1:15, or 1:3 to1:10, or 1:4 to 1:8.

Adding electrodes to the first group of electrodes operating in the modewith the first polarity may significantly reduce the intensity of theelectric field near the electrodes. Using four electrodes instead of onefor example in the first group of electrodes operating in the mode withthe first polarity, the intensity of the electric field at the electrodesurface decreases by a factor of four, while in examples where threeelectrodes are used, the intensity of the electric field decreases by afactor of two. This reduction in intensity may allow for the use oflower voltage on the electrodes, compared to a solution with just oneelectrode operating in the mode with the first polarity. The reductionmay additionally or alternatively increase of the depth of the ablatedtarget tissue by increasing an area of the electric field with a certainvoltage per cm². The value of the voltage per cm² in an area of theelectric field may be for example from 50 V/cm² to 3000 V/cm², or from100 V/cm² to 1500 V/cm², or from 250 V/cm² to 1000 V/cm².

The particular electrodes on the catheter distal tip can be switched toone or more than one of the modes during the ablation. They can beswitched during one ablation cycle or during several ablation cycles.The electrodes may be switched to one or more of the modes several timesduring one ablation cycle or during several ablation cycles. In someaspects it is even possible to have two or more groups of electrodesoperating simultaneously in a mode with the first polarity and a groupof electrodes operating in a different polarity, with or withoutelectrodes operating in a state of high impedance.

A layout or spatial pattern of the electrodes on the distal tip may becreated with a consideration of the hybrid mode of operation ofelectrodes and/or with the goal of creating virtual electrodes. Becausethe electrodes may be switched to one or more than one of the modesduring the ablation, it is possible the resulting virtual electrodes mayhave different spatial shapes which means the electric fields createdaround and between the virtual electrodes may have different shapes withdifferent structures of the magnetic field and/or different density andintensity of the electric field. An example of a spatial pattern ofelectrodes on the distal tip, specifically on the expandable basket maybe seen in FIG. 13A and in FIG. 13B. FIG. 13A shows a frontal view ofthe basket assembly (401) with a spatial pattern of electrodes (109)suitable for creation of virtual electrodes by switching the electrodes(109) into different modes of operation with the first polarity and withthe different polarity and/or with a state of high impedance.

FIG. 13B shows again a frontal view of the basket assembly (401) with aspatial pattern of electrodes suitable for creation of virtualelectrodes, by switching the electrodes (109) into different modes,however this time the electrodes are placed in areas where the filaments(415) cross each other (filaments crossing points).

One possible layout of electrodes already switched into the hybridoperation mode may be seen in the FIG. 14 , which is again a frontalview of the basket assembly (401). A first group of electrodes (109) isoperating in the mode with a first polarity (P1) and together creates afirst virtual electrode (1401). Another group of electrodes (109) isoperating in the mode with a different polarity (P2) and togethercreates a second virtual electrode (1403). When electrical pulses aredelivered from the pulse generator (103) to the electrodes (109) in thisconfiguration, electric fields will be created between and around thevirtual electrodes (1401, 1403). Some of the electrodes (109) may beoperating in a third mode, for example in a state of high impedance(HI).

The electrodes in a state of high impedance (higher than 500Ω) may helpin shaping an electric field created among and around electrodes fromthe first group and the second group of electrodes and/or between oraround the virtual electrodes. In one example, assigning a state of highimpedance to electrodes which are spatially adjacent to the electrodesoperating in the mode with a first polarity may have a positive effecton the shape of the electric field in a way that a portion of theelectric field which is able to cause an ablation reaches deeper intothe target tissue of the treatment site, compared to an operation modewithout electrodes in a state of high impedance. This phenomenon mayhave positive effects in the quality and homogeneity of an ablationprocedure. The electrodes in a state of high impedance may be spatiallyplaced between the first group of electrodes and the second group ofelectrodes.

An exemplary pattern of electrodes (109) is displayed in more detail inFIG. 15A. The electrodes (109) create a pattern of repeating crosses orsquares or rectangles on the filaments (415) of the braided mesh in oneof the expanded configurations of the expandable basket. From this view,which is perpendicular to the tangent plane (which is touching theexpandable basket for example at an intersection (1501) of fourneighboring electrodes), the pattern seems two-dimensional, but inreality, it is three-dimensional, because the electrodes (109) are fixedto, or are part of the filaments (415) of the braided mesh, whichcreates an expandable basket, and therefore the pattern fits into thecurvature of the expandable basket. This pattern of the electrodes isadvantageous in embodiments using a group of electrodes operating in amode with first polarity (P1). In this example a group of four adjacentelectrodes operating in a mode with first polarity (P1) and hencecreating a first virtual electrode (1401) will have either a crossshape, as indicated in FIG. 15A or a square or rectangle shape asindicated in FIG. 15B. The advantage is that both virtual electrodes(1401) created by both shapes are, in combination with a second virtualelectrode, and possibly with the help of the electrodes in a state ofhigh impedance, capable of creating electric fields having certainqualities (shape, magnitude, density, gradient of potential) suitablefor the ablation of a target tissue.

FIG. 15C shows an example of a pattern of electrodes where theelectrodes (109) are placed in areas where the filaments (415) crosseach other (filament crossing points). An exemplary group of electrodesoperating in a mode with first polarity (P1) is also shown here.

The exact shape of the pattern of electrodes partially depends on theshape of the expandable basket. It also means the pattern and the shapeof the groups of electrodes creating the virtual electrodes may bedifferent in a collapsed configuration and/or in different expandedconfigurations of the expandable basket. For most of the expandedconfigurations of the expandable basket, the rectangles and squarescreated by the electrodes as described above will be inclined and willbe creating shapes closer to rhombuses or rhomboids. The same applies tothe angles between the two imaginary lines creating a cross and passingthrough the electrodes, which will not be right angles in most of theexpanded configurations.

When using high voltage pulses in the human body, it may be necessary tosynchronize the delivery of the pulses with a cardiac cycle for safetyreasons, for example in order to avoid ventricular rhythm. The pulsedfield ablation device can incorporate or use a means for such asynchronization including triggering of the pulse delivery by thissynchronization means. The synchronization means can be for example anECG device.

1-32. (canceled)
 33. An ablation device for pulsed field ablation of a tissue by pulsed electric field, the device comprising: a catheter configured for insertion into a heart of a patient comprising a set of electrodes; and a pulse generator configured to generate electric pulses, the pulse generator electrically coupled to the set of electrodes; wherein the set of electrodes is configured to provide pulsed electric fields from the electric pulses causing ablation of a tissue within the heart of the patient; wherein the set of electrodes comprises a first electrode configured for operation in a mode of a first polarity, a second electrode configured for operation in a mode of a second polarity different than the first polarity, and a third electrode configured for operation in a mode of a state of high impedance; and wherein the set of electrodes comprises at least one electrode configured to be switched between at least two of the modes during an ablation.
 34. The ablation device according to claim 33, wherein the third electrode is configured for operation in a mode of a state of impedance higher than 500Ω.
 35. The ablation device according to claim 33, wherein a ratio of a surface area of the first electrode to a surface area of the second electrode is in a range from 2:3 to 1:100.
 36. The ablation device according to claim 33, wherein the set of electrodes comprises at least two second electrodes configured for operation in the mode of the second polarity different than the first polarity.
 37. The ablation device according to claim 36, wherein the set of electrodes comprises at least two third electrodes configured for operation in the mode of the state of high impedance.
 38. The ablation device according to claim 36, wherein a ratio of a surface area or sum of the surface areas of the at least one first electrode to a sum of a surface areas of the at least two second electrodes is in a range from 2:3 to 1:100.
 39. The ablation device according to claim 33, wherein the third electrode is spatially adjacent to the first electrode.
 40. A catheter for pulsed field ablation of a tissue by pulsed electric field, the catheter configured for insertion into a heart of a patient comprising: a set of electrodes; the set of electrodes configured to provide pulsed electric fields causing ablation of a tissue within the heart of the patient; wherein the set of electrodes comprises a first electrode configured for operation in a mode of a first polarity, a second electrode configured for operation in a mode of a second polarity different than the first polarity, and a third electrode configured for operation in a mode of a state of high impedance; and wherein the set of electrodes comprises at least one electrode configured to be switched between at least two of the modes during an ablation.
 41. The catheter according to claim 40, wherein the third electrode is configured for operation in a mode of a state of impedance higher than 500Ω.
 42. The catheter according to claim 40, wherein a ratio of a surface area of the first electrode to a surface area of the second electrode is in a range from 2:3 to 1:100.
 43. The catheter according to claim 40, wherein the set of electrodes comprises at least two second electrodes configured for operation in the mode of the second polarity different than the first polarity.
 44. The catheter according to claim 43, wherein the set of electrodes comprises at least two third electrodes configured for operation in the mode of the state of high impedance.
 45. The catheter according to claim 43, wherein a ratio of a surface area or sum of the surface areas of the at least one first electrode to a sum of a surface areas of the at least two second electrodes is in a range from 2:3 to 1:100.
 46. The catheter according to claim 40, wherein the third electrode is spatially adjacent to the first electrode.
 47. A catheter for pulsed field ablation of a tissue by pulsed electric field, the catheter configured for insertion into a heart of a patient; wherein the catheter comprising a set of electrodes couplable to a pulse generator, wherein the pulse generator is configured to generate electric pulses; the set of electrodes configured to provide pulsed electric fields from the electric pulses causing ablation of a tissue within the heart of the patient; wherein the set of electrodes comprises a first electrode configured for operation in a mode of a first polarity, a second electrode configured for operation in a mode of a second polarity different than the first polarity, and a third electrode configured for operation in a mode of a state of high impedance; and wherein the set of electrodes comprises at least one electrode configured to be switched between at least two of the modes during an ablation.
 48. The catheter according to claim 47, wherein the third electrode is configured for operation in a mode of a state of impedance higher than 500Ω.
 49. The catheter according to claim 47, wherein a ratio of a surface area of the first electrode to a surface area of the second electrode is in a range from 2:3 to 1:100.
 50. The catheter according to claim 47, wherein the set of electrodes comprises at least two second electrodes configured for operation in the mode of the second polarity different than the first polarity.
 51. The catheter according to claim 50, wherein the set of electrodes comprises at least two third electrodes configured for operation in the mode of the state of high impedance and wherein a ratio of a surface area or sum of the surface areas of the at least one first electrode to a sum of a surface areas of the at least two second electrodes is in a range from 2:3 to 1:100.
 52. The catheter according to claim 47, wherein the third electrode is spatially adjacent to the first electrode.
 53. The catheter according to claim 47, wherein the catheter is configured to be manipulated from a collapsed configuration to at least one expanded configuration.
 54. The catheter according to claim 47, wherein the catheter comprising an expandable basket; and wherein the set of electrodes is positioned on the basket.
 55. The catheter according to claim 54, wherein the expandable basket comprising a plurality of filaments comprising an electrically non-conductive material; and wherein the set of electrodes is positioned on the plurality of filaments.
 56. An ablation device for pulsed field ablation of a tissue by pulsed electric field, the device comprising: a pulse generator configured to generate electric pulses, the pulse generator configured to be electrically coupled to a set of electrodes configured to provide pulsed electric fields from the electric pulses, the pulsed electric fields configured to cause an ablation of a tissue within a heart of a patient; wherein the device is configured to switch a first electrode from the set of electrodes to a mode with a first polarity, a second electrode from the set of electrodes to a mode with a second polarity different than the first polarity, and a third electrode from the set of electrodes to a mode of a state of a high impedance; and wherein the device is configured to switch at least one electrode from the set of electrodes between at least two of the modes during an ablation.
 57. The ablation device according to claim 56, wherein an impedance in the mode of a state of a high impedance is higher than 500Ω.
 58. The ablation device according to claim 56, wherein a ratio of a surface area of the first electrode to a surface area of the second electrode is in a range from 2:3 to 1:100.
 59. The ablation device according to claim 56, wherein the device is configured to switch at least two second electrodes from the set of electrodes to the mode of the second polarity different than the first polarity.
 60. The ablation device according to claim 59, wherein the device is configured to switch at least two third electrodes from the set of electrodes to a mode of state of a high impedance.
 61. The ablation device according to claim 59, wherein a ratio of a surface area or sum of the surface areas of the at least one first electrode to a sum of a surface areas of the at least two second electrodes is in a range from 2:3 to 1:100.
 62. The ablation device according to claim 56, wherein the third electrode is spatially adjacent to the first electrode. 